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Key Features

Essentials of Diagnosis

  • Prolonged fever

  • Exudative pharyngitis

  • Generalized adenopathy

  • Hepatosplenomegaly

  • Atypical lymphocytes

  • Heterophil antibodies

General Considerations

  • Mononucleosis is the most characteristic syndrome produced by EBV infection

  • Young children infected with EBV have either no symptoms or a mild nonspecific febrile illness

  • In older patients, EBV infection is more likely to produce the typical features of the mononucleosis syndrome

  • EBV is acquired readily from asymptomatic carriers and from recently ill patients

  • Young children are infected from the saliva of playmates and family members

  • Adolescents may be infected through sexual activity

  • EBV can also be transmitted by blood transfusion and organ transplantation

Clinical Findings

Symptoms and Signs

  • Incubation period of 1–2 months

  • A 2- to 3-day prodrome of malaise and anorexia yields, abruptly or insidiously, to a febrile illness with temperatures exceeding 39°C

  • Lymph nodes are enlarged, firm, and mildly tender

  • Rash is present in 5% of patients

    • Can be macular, scarlatiniform, or urticarial

    • Almost universal in patients taking penicillin or ampicillin

  • Soft palate petechiae and eyelid edema are also observed

Differential Diagnosis

  • Group A streptococcal infection

  • Bacterial infection

  • Severe primary herpes simplex pharyngitis

  • Adenoviruses

  • Serum sickness–like drug reactions and leukemia

  • Cytomegalovirus mononucleosis


  • Leukopenia may occur early, but an atypical lymphocytosis (comprising over 10% of the total leukocytes at some time in the illness) is most notable

  • Hematologic changes may not be seen until the third week of illness and may be entirely absent in some EBV syndromes (eg, neurologic)

  • Heterophile antibodies

    • Appear in over 90% of older patients with mononucleosis, but in less than 50% of children younger than age 5 years

    • May not be detectable until the second week of illness

    • May persist for up to 12 months after recovery

    • Rapid screening tests (slide agglutination) are usually positive if the titer is significant

    • Positive result strongly suggests but does not prove EBV infection

  • Acute EBV infection is established by detecting IgM antibody to the viral capsid antigen (VCA) or by detecting a fourfold or greater change of IgG anti-VCA titers

  • Detection of EBV DNA is the method of choice for the diagnosis of CNS and ocular infections


  • Bed rest may be necessary in severe cases

  • Acetaminophen controls high fever

  • Potential airway obstruction due to swollen pharyngeal lymphoid tissue responds rapidly to systemic corticosteroids

  • Acyclovir, valacyclovir, penciclovir, ganciclovir, and foscarnet are indicated for chronic active EBV



  • Patients with splenic enlargement should avoid contact sports for 6–8 weeks


  • Splenic rupture is rare, usually following significant trauma

  • Hematologic complications, including hemolytic anemia, thrombocytopenia, and neutropenia, are more ...

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